# PROTACs & molecular glues (targeted protein degradation)

Source: https://onco.cc/technologies/protac-degrader/  
OnCo record `protac-degrader` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Instead of blocking a protein, these drugs tag it for the cell's own garbage disposal, removing it entirely.

## Summary

Vepdegestrant (Veppanu, Arvinas/Pfizer), an oral ER PROTAC, became the first approved PROTAC in 2026 for ESR1-mutant HR+ breast cancer (VERITAC-2). Molecular glues (lenalidomide, pomalidomide, and next-generation CELMoDs iberdomide, mezigdomide) are established in myeloma. Degraders of AR, BTK, BCL6, KRAS, IKZF1/3, and the 'undruggable' transcription factors are in the clinic. Degrader-antibody conjugates deliver them selectively.

## Fields

- Kind: Technology
- Status: approved
- Last checked: 2026-09-04
- Principle: Bifunctional molecule recruits an E3 ubiquitin ligase (cereblon, VHL) to the target, causing ubiquitination and proteasomal destruction.
- Since: 2026
- Strengths: Event-driven (catalytic), removes scaffolding functions; Reaches non-enzymatic targets
- Limitations: Large molecules with poor oral bioavailability (PROTACs); Hook effect; E3 ligase expression varies

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Proteolysis_targeting_chimera
- Wikipedia: https://en.wikipedia.org/wiki/Proteolysis_targeting_chimera

## Connected records

- ideas: [An open degrader consortium against every undruggable driver transcription factor](https://onco.cc/ideas/idea-moon-open-degrader-consortium/), [An open-science consortium on the undruggable drivers, open until a candidate](https://onco.cc/ideas/idea-fund-precompetitive-undruggable-consortium/), [Attack the backup copy when a tumour has lost the original gene](https://onco.cc/ideas/idea-bio1-paralog-synthetic-lethality/), [BTK degraders to pre-empt resistance in frontline CLL](https://onco.cc/ideas/idea-btk-degrader-frontline/), [Degrade the damaged p53 protein rather than trying to repair it](https://onco.cc/ideas/idea-bio1-mutant-p53-degrader/), [Degraders for the fusion proteins that drive childhood sarcomas](https://onco.cc/ideas/idea-bio1-fusion-tf-degraders/), [Design protein degraders small enough to get into the brain](https://onco.cc/ideas/idea-bio2-brain-penetrant-glue-degraders/), [Destroy the truncated androgen receptor that hormone drugs cannot touch](https://onco.cc/ideas/idea-bio1-arv7-degrader/), [Drag cancer's surface and secreted proteins to the cell's recycling bin](https://onco.cc/ideas/idea-bio1-lytac-surface-degraders/), [Find E3 ligases that only tumours have, and build degraders around them](https://onco.cc/ideas/idea-bio1-tumour-restricted-e3-atlas/), [Instruct tumour cells to make antibodies against their own oncoprotein](https://onco.cc/ideas/idea-bio1-mrna-intrabodies/), [Molecular glues that break the MYC-MAX partnership](https://onco.cc/ideas/idea-bio1-myc-max-molecular-glue/), [One-two punch: clear senescent cells after chemotherapy](https://onco.cc/ideas/idea-senolytics-after-chemo/), [Screen glue-like compounds against every cancer cell line and publish it](https://onco.cc/ideas/idea-bio1-glue-degrader-atlas/), [Use antibodies to deliver protein-destroying drugs into the right cells](https://onco.cc/ideas/idea-bio1-antibody-degrader-conjugates/)
- companies: [Amphista Therapeutics](https://onco.cc/companies/amphista-therapeutics/), [Arvinas](https://onco.cc/companies/arvinas/), [Boundless Bio](https://onco.cc/companies/boundless-bio/), [Bristol Myers Squibb](https://onco.cc/companies/bms/), [C4 Therapeutics](https://onco.cc/companies/c4-therapeutics/), [Captor Therapeutics](https://onco.cc/companies/captor-therapeutics/), [Cullgen](https://onco.cc/companies/cullgen/), [Firefly Bio](https://onco.cc/companies/firefly-bio/), [Foghorn Therapeutics](https://onco.cc/companies/foghorn-therapeutics/), [Kymera Therapeutics](https://onco.cc/companies/kymera/), [Monte Rosa Therapeutics](https://onco.cc/companies/monte-rosa/), [Neomorph](https://onco.cc/companies/neomorph/), [Nurix Therapeutics](https://onco.cc/companies/nurix/), [Orum Therapeutics](https://onco.cc/companies/orum-therapeutics/), [Pathos AI](https://onco.cc/companies/pathos-ai/), [Pfizer (incl. Seagen)](https://onco.cc/companies/pfizer/), [Photys Therapeutics](https://onco.cc/companies/photys-therapeutics/), [Plexium](https://onco.cc/companies/plexium/), [Prelude Therapeutics](https://onco.cc/companies/prelude-therapeutics/), [Proxygen](https://onco.cc/companies/proxygen/), [Recursion Pharmaceuticals](https://onco.cc/companies/recursion/), [Stablix](https://onco.cc/companies/stablix/), [Treeline Biosciences](https://onco.cc/companies/treeline-biosciences/), [Triana Biomedicines](https://onco.cc/companies/triana-biomedicines/), [Wigen Biomedicine Technology (Shanghai)](https://onco.cc/companies/wigen-biomedicine-technology-shanghai/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- technologies: [Degrader-antibody conjugate (DAC)](https://onco.cc/technologies/degrader-antibody-conjugate/), [Endocrine therapy (SERMs, AIs, SERDs)](https://onco.cc/technologies/endocrine-therapy/), [High-throughput screening and DNA-encoded libraries](https://onco.cc/technologies/high-throughput-screening-libraries/), [Molecular glue discovery platforms](https://onco.cc/technologies/molecular-glue-platforms/), [Structural biology infrastructure (cryo-EM, synchrotrons, AlphaFold)](https://onco.cc/technologies/structural-biology-infrastructure/)
- targets: [Androgen receptor](https://onco.cc/targets/androgen-receptor/), [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/), [EWSR1-FLI1 fusion](https://onco.cc/targets/ewsr1-fli1/), [KRAS](https://onco.cc/targets/kras/), [MDM2](https://onco.cc/targets/mdm2/)
- drugs: [BGB-16673](https://onco.cc/drugs/bgb-16673/), [Golcadomide](https://onco.cc/drugs/golcadomide/), [Iberdomide](https://onco.cc/drugs/iberdomide/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/), [Mezigdomide](https://onco.cc/drugs/mezigdomide/), [Pomalidomide](https://onco.cc/drugs/pomalidomide/), [Thalidomide](https://onco.cc/drugs/thalidomide/), [Vepdegestrant](https://onco.cc/drugs/vepdegestrant/)
- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Ewing sarcoma](https://onco.cc/cancers/ewing-sarcoma/), [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/)
- trials: [A Dose-Escalation and Expansion Study of Tacabrutideg (BGB-16673) in Participants With B-Cell Malignancies](https://onco.cc/trials/nct05006716/), [A Novel Vaccine (EO2463) as Monotherapy and in Combination, for Treatment of Patients With Indolent Non-Hodgkin Lymphoma](https://onco.cc/trials/nct04669171/), [A Phase 1b/2 Study of Sonrotoclax (BGB-11417) as Monotherapy and in Various Combinations With Dexamethasone Plus Carfilzomib, Dexamethasone Plus Darat](https://onco.cc/trials/nct04973605/), [A Phase 3 Study to Assess Efficacy and Safety of Tafasitamab Plus Lenalidomide and Rituximab Compared to Placebo Plus Lenalidomide and Rituximab in Pa](https://onco.cc/trials/nct04680052/), [A Study Comparing Talquetamab in Combination With Daratumumab or in Combination With Daratumumab and Pomalidomide Versus Daratumumab in Combination Wi](https://onco.cc/trials/nct05455320/), [A Study Comparing Talquetamab Plus Pomalidomide, Talquetamab Plus Teclistamab, and Elotuzumab, Pomalidomide, and Dexamethasone or Pomalidomide, Bortez](https://onco.cc/trials/nct06208150/), [A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With](https://onco.cc/trials/nct05572515/), [A Study Designed to Evaluate the Safety and Efficacy of Venetoclax Plus Dexamethasone (VenDex) Compared With Pomalidomide Plus Dexamethasone (PomDex) ](https://onco.cc/trials/nct03539744/), [A Study Evaluating the Efficacy and Safety of Mosunetuzumab in Combination With Lenalidomide in Comparison to Rituximab in Combination With Lenalidomi](https://onco.cc/trials/nct04712097/), [A Study Evaluating the Safety, Pharmacokinetics, and Efficacy of Mosunetuzumab + Lenalidomide (+Len), and the Safety, Tolerability, and Pharmacokineti](https://onco.cc/trials/nct04246086/), [A Study of Belantamab Mafodotin Administered in Combination With Lenalidomide and Dexamethasone (BRd) Versus Daratumumab, Lenalidomide, and Dexamethas](https://onco.cc/trials/nct06679101/), [A Study of BGB-16673 Compared to Investigator's Choice in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Previously Exposed to Covalent Bruton Tyrosine Kinase (BTK) Inhibitors](https://onco.cc/trials/nct06970743/), [A Study of Different Sequences of Cilta-cel, Talquetamab in Combination With Daratumumab and Teclistamab in Combination With Daratumumab Following Ind](https://onco.cc/trials/nct06577025/), [A Study of Subcutaneously Injected Epcoritamab Plus Oral Lenalidomide Tablets Compared to Intravenously (IV) Infused Rituximab Plus IV Infused Gemcita](https://onco.cc/trials/nct06508658/), [A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal](https://onco.cc/trials/nct05552222/), [A Study of the Efficacy and Safety of BCD-248 in Combination With Daratumumab in Patients With Relapsed or Refractory Multiple Myeloma (AMMADINA)](https://onco.cc/trials/nct07742215/), [A Study of Zanubrutinib Plus Anti-CD20 Versus Lenalidomide Plus Rituximab in Participants With Relapsed/Refractory Follicular or Marginal Zone Lymphom](https://onco.cc/trials/nct05100862/), [A Study to Assess A Change in Disease Activity and Adverse Events of Intravenous Etentamig and Daratumumab (Etentamig+D) Compared to Daratumumab, Lena](https://onco.cc/trials/nct07095452/), [A Study to Assess Safety and Efficacy of CHO-H01 as a Single Agent/Combined With Lenalidomide in Subjects With Refractory or Relapsed Non-Hodgkin's Ly](https://onco.cc/trials/nct05950165/), [A Study to Assess the Efficacy, Safety, Pharmacodynamics, and Pharmacokinetics of Tazemetostat in Combination With Lenalidomide Plus Rituximab Versus ](https://onco.cc/trials/nct04224493/), [A Study to Compare Iberdomide Maintenance Versus Lenalidomide Maintenance Therapy Following Autologous Stem Cell Transplant in Participants With Newly](https://onco.cc/trials/nct05827016/), [A Study to Compare the Efficacy and Safety of Golcadomide in Combination With Rituximab (Golca + R) vs Investigator's Choice in Participants With Rela](https://onco.cc/trials/nct06911502/), [A Study to Compare the Efficacy and Safety of Idecabtagene Vicleucel With Lenalidomide Maintenance Therapy Versus Lenalidomide Maintenance Therapy Alo](https://onco.cc/trials/nct06045806/), [A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple](https://onco.cc/trials/nct02773030/), [A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Tre](https://onco.cc/trials/nct03989414/), [A Study to Determine the Recommended Dose and Schedule, and Evaluate the Safety and Preliminary Efficacy of Mezigdomide in Combination With Elranatama](https://onco.cc/trials/nct06988488/), [A Study to Evaluate Mezigdomide in Combination With Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants W](https://onco.cc/trials/nct05552976/), [A Study to Evaluate Mezigdomide, Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Participants With Re](https://onco.cc/trials/nct05519085/), [A Study to Evaluate Safety, Drug Levels and Effectiveness of CC-92480 (BMS-986348) in Combination With Other Treatments in Participants With Relapsed ](https://onco.cc/trials/nct05372354/), [A Study to Evaluate the Efficacy and Safety of Golcadomide in Combination With Rituximab in Participants With Newly Diagnosed Advanced Stage Follicular Lymphoma](https://onco.cc/trials/nct06425302/), [A Study to Learn About the Effects of the Combination of Elranatamab, Daratumumab and Lenalidomide Compared With Daratumumab, Bortezomib, Lenalidomide](https://onco.cc/trials/nct05623020/), [A Study to Learn About the Study Medicine Elranatamab Alone and With Daratumumab in People With Multiple Myeloma Who Have Received Other Treatments](https://onco.cc/trials/nct05020236/), [A Study to Learn About Vepdegestrant When Given With PF-07220060 to People With Advanced or Metastatic Breast Cancer.](https://onco.cc/trials/nct06206837/), [A Trial to Find Out if Odronextamab Combined With Lenalidomide is Safe and Works Better Than Rituximab Combined With Lenalidomide in Adult Participant](https://onco.cc/trials/nct06149286/), [A Trial to Learn How Well Linvoseltamab Works Compared to the Combination of Elotuzumab, Pomalidomide and Dexamethasone for Adult Participants With Re](https://onco.cc/trials/nct05730036/), [All Japanese Population: Belantamab Mafodotin Plus Pomalidomide and Dexamethasone (Pd) Versus Bortezomib Plus Pd in Relapsed/Refractory Multiple Myelo](https://onco.cc/trials/nct06956170/), [AUGMENT](https://onco.cc/trials/augment/), [Brentuximab Vedotin Plus Lenalidomide and Rituximab for the Treatment of Relapsed/Refractory DLBCL](https://onco.cc/trials/nct04404283/), [CaDAnCe-304](https://onco.cc/trials/cadance-304/), [DETERMINATION](https://onco.cc/trials/determination/), [Efficacy and Safety of Orelabrutinib Combined With Rituximab Versus Lenalidomide Combined With Rituximab in Patients With Relapsed/Refractory Marginal Zone Lymphoma](https://onco.cc/trials/nct06082102/), [GOLSEEK-1](https://onco.cc/trials/golseek-1/), [IFM 2009](https://onco.cc/trials/ifm-2009/), [Isatuximab in Combination With Lenalidomide and Dexamethasone in High-risk Smoldering Multiple Myeloma](https://onco.cc/trials/nct04270409/), [MagnetisMM-32: A Study to Learn About the Study Medicine Called Elranatamab in People With Multiple Myeloma (MM) That Has Come Back After Taking Other](https://onco.cc/trials/nct06152575/), [MIL62 Plus Lenalidomide for Patients With Relapsed/Refractory Indolent Non-Hodgkin's Lymphoma (FL and MZL)](https://onco.cc/trials/nct04110301/), [Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants ](https://onco.cc/trials/nct04975997/), [Safety and Pharmacokinetics Study of a Modified Tafasitamab IV Dosing Regimen Combined With Lenalidomide in R-R DLBCL Patients](https://onco.cc/trials/nct05222555/), [Safety, Efficacy, and Pharmacokinetics of Continuous Subcutaneous Lenalidomide in Multiple Myeloma (MM)](https://onco.cc/trials/nct06087653/), [Study of Selinexor Plus DRd for Newly Diagnosed Multiple Myeloma](https://onco.cc/trials/nct04782687/), [Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease ](https://onco.cc/trials/nct06191744/), [Study of Subcutaneous Epcoritamab in Combination With Intravenous Rituximab and Oral Lenalidomide (R2) to Assess Adverse Events and Change in Disease ](https://onco.cc/trials/nct05409066/), [Study to Evaluate the Safety and Efficacy of Tafasitamab Plus Lenalidomide in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (](https://onco.cc/trials/nct05429268/), [Study With Elranatamab Versus Lenalidomide in Patients With Newly Diagnosed Multiple Myeloma After Transplant](https://onco.cc/trials/nct05317416/), [Sub-study of Belantamab Mafodotin (GSK2857916) as Monotherapy and in Combination With Nirogacestat, Pomalidomide, and Dexamethasone in Participants Wi](https://onco.cc/trials/nct07150104/), [Sub-study of Belantamab Mafodotin (GSK2857916) in Combination With Nirogacestat, Lenalidomide, and Dexamethasone in Participants With RRMM](https://onco.cc/trials/nct07150091/), [TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study A)](https://onco.cc/trials/nct05548127/), [TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer (Sub-Study B)](https://onco.cc/trials/nct05573555/), [TACTIVE-U: A Study to Learn About the Study Medicine (Vepdegestrant) When Given With Other Medicines in People With Advanced or Metastatic Breast Cancer. (Sub-Study C)](https://onco.cc/trials/nct06125522/), [To Assess the Safety and Tolerability of Tafasitamab Alone or in Combination With Other Drugs in Japanese Participants With Non-Hodgkins Lymphoma (NHL](https://onco.cc/trials/nct04661007/), [Treatment of Chinese Participants With B-Cell Malignancies With BGB-16673, a Bruton Tyrosine Kinase-Targeted Protein-Degrader](https://onco.cc/trials/nct05294731/), [Vepdegestrant (ARV-471/PF-07850327) + Palbociclib vs Letrozole + Palbociclib in ER(+)/HER2(-) Advanced Breast Cancer](https://onco.cc/trials/nct05909397/), [VERITAC-2](https://onco.cc/trials/veritac-2/)
- institutions: [Laura and Isaac Perlmutter Cancer Center at NYU Langone Health](https://onco.cc/institutions/nyu-perlmutter/), [Rambam Health Care Campus](https://onco.cc/institutions/rambam/), [Technion, Israel Institute of Technology](https://onco.cc/institutions/technion/), [University of Michigan Rogel Cancer Center](https://onco.cc/institutions/michigan-rogel/)
- pathways: [Oestrogen receptor signalling](https://onco.cc/pathways/er-signaling/), [SWI/SNF chromatin remodelling](https://onco.cc/pathways/swi-snf-chromatin/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/), [Ubiquitin-proteasome system & protein homeostasis](https://onco.cc/pathways/ubiquitin-proteasome-system/)
- people: [Aaron Ciechanover](https://onco.cc/people/aaron-ciechanover/), [Avram Hershko](https://onco.cc/people/avram-hershko/), [Benjamin L. Ebert](https://onco.cc/people/benjamin-ebert/), [Jennifer R. Brown](https://onco.cc/people/jennifer-brown/), [Komal Jhaveri](https://onco.cc/people/komal-jhaveri/), [Moshe Oren](https://onco.cc/people/moshe-oren/), [Shaomeng Wang](https://onco.cc/people/shaomeng-wang/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [The undruggable drivers](https://onco.cc/bottlenecks/b-undruggable-targets/), [The valley of death between lab and product](https://onco.cc/bottlenecks/b-translational-valley/)
- key papers: [The first PROTAC: a chimeric molecule that tags a protein for destruction](https://onco.cc/key-papers/paper-protac-concept-sakamoto-pnas-2001/), [Veber 2002: molecular properties that influence the oral bioavailability of drug candidates](https://onco.cc/key-papers/paper-veber-oral-bioavailability-jmedchem-2002/)
- terms: [Immunomodulatory drugs (IMiDs) and CELMoDs](https://onco.cc/terms/imid/), [Inhibitor](https://onco.cc/terms/inhibitor/), [Selective oestrogen receptor degrader (SERD)](https://onco.cc/terms/serd/), [Small molecule drug](https://onco.cc/terms/small-molecule/)
- roadmaps: [Drug discovery roadmap: screening in mice → maps of dependency → designing in silico](https://onco.cc/roadmaps/drug-discovery-roadmap/), [Epigenetic therapy roadmap: loosening silenced genes → mutation-specific enzymes → editing the epigenome](https://onco.cc/roadmaps/epigenetics-roadmap/), [Hormonal therapy roadmap: removing the ovaries → tamoxifen → oral degraders switched by a blood test](https://onco.cc/roadmaps/hormonal-therapy-roadmap/), [Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall](https://onco.cc/roadmaps/targeted-therapy-roadmap/)

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